Novel capillary electrophoresis methods using CDs as chiral selectors were developed and validated for the chiral separation of lansoprazole and rabeprazole, two proton pump inhibitors. Fourteen different neutral and anionic CDs were screened at pH 4 and 7 in the preliminary analysis. Sulfobutyl-ether-β-CD with a degree of substitution of 6.5 and 10 at neutral pH proved to be the most suitable chiral selector for both compounds. Various dual CD systems were also compared, and the possible mechanisms of enantiomer separation were investigated. A dual selector system containing sulfobutyl-ether-β-CD degree of substitution 6.5 and native γ-CD proved to be the most adequate system for the separations. Method optimization was carried out using an experimental design approach, performing an initial fractional factorial screening design, followed by a central composite design to establish the optimal analytical conditions. The optimized methods (25 mM phosphate buffer, pH 7, 10 mM sulfobutyl-ether-β-CD/20 mM γ-CD, +20 kV voltage; 17°C temperature; 50 mbar/3 s injection, detection at 210 nm for lansoprazole; 25 mM phosphate buffer, pH 7, 15 mM sulfobutyl-ether-β-CD/30 mM γ-CD, +20 kV voltage; 18°C temperature; 50 mbar/3 s injection, detection at 210 nm for rabeprazole) provided baseline separation for lansoprazole (Rs = 2.91) and rabeprazole (Rs = 2.53) enantiomers with favorable migration order (in both cases the S-enantiomers migrates first). The optimized methods were validated according to current guidelines and proved to be reliable, linear, precise, and accurate for the determination of 0.15% distomer as chiral impurity in dexlansoprazole and dexrabeprazole samples.
- MeSH
- Cyclodextrins chemistry MeSH
- Electrophoresis, Capillary methods MeSH
- Lansoprazole analysis chemistry isolation & purification MeSH
- Limit of Detection MeSH
- Linear Models MeSH
- Rabeprazole analysis chemistry isolation & purification MeSH
- Reproducibility of Results MeSH
- Stereoisomerism MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Gastroesophageal Reflux drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Diarrhea * chemically induced MeSH
- Rabeprazole * administration & dosage adverse effects MeSH
- Tinnitus * chemically induced MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Hlavními medikamenty v léčbě acidopeptických onemocnění jsou inhibitory protonové pumpy (IPP). Všechny IPP jsou slabé zásady selektivně se metabolizující v kyselém prostředí a blokující funkci aktivní protonové pumpy. IPP poskytují účinnou léčbu u refluxní nemoci jícnu, eradikace Helicobacter pylori, funkční dyspepsie a gastropatie z nesteroidních antirevmatik. Jsou také součástí léčby u eozinofilní ezofagitidy. IPP první generace zahrnují omeprazol, pantoprazol a lansoprazol, druhé generace esomeprazol a rabeprazol. IPP se liší ve farmakokinetických charakteristikách, tyto rozdíly však nemusí mít klinicky relevantní důsledky. Obecně IPP druhé generace zajišťují rychlejší nástup účinku, protrahovanější inhibici žaludeční sekrece a zejména účinek rabeprazolu je méně závislý na způsobu podávání a méně ovlivňuje funkce cytochromu P450. Účinnost IPP zejména první generace ovlivňuje genetická variabilita enzymu CYP2C19 a je významně nižší u rychlých metabolizátorů. IPP jsou velmi bezpečné a bezprostřední komplikace jsou výjimečné. U helikobakterové infekce vedou k progresi gastrititidy. Přestože způsobují hypergastrinemii, nevykazují IPP maligní potenciál. Jejich dlouhodobé podávání je spojeno s vyšším rizikem fraktur páteře a kyčlí, komunitních pneumonií a klostridiové střevní infekce. Mohou vést ke snížení účinnosti antiagregační léčby s klopidogrelem se zvýšeným rizikem recidivujících kardiovaskulárních příhod, což neplatí pro prasugrel. V nejbližší době nelze očekávat v jiných molekulách či lékových úpravách zásadní pokrok. Příbalové letáky jsou vesměs nevhodně konstruovány a chybí v nich často zásadní informace. Klíčová slova: inhibitory protonové pumpy – omeprazol – lansoprazol – pantoprazol – rabeprazol – esomeprazol – vedlejší účinky – interakce
Proton pump inhibitors (PPI) are the primary medication in the treatment of acid-related diseases. All proton pump inhibitors are weak bases selectively metabolised in an acid environment which block the function of active proton pumps. Proton pump inhibitors provide efficient treatment for gastroesophageal reflux disease, Helicobacter pylori, functional dyspepsia and NSAID gastropathy. PPI may be helpful in patients with eosinophilic oesophagitis. PPI of the first generation comprise omeprazole, pantoprazole and lansoprazole, the second one is represented by esomeprazole and rabeprazole. Proton pump inhibitors differ in pharmacokinetic properties but these differences do not necessarily have clinically relevant consequences. Generally, second generation proton pump inhibitors provide a faster onset of effect, longer gastric secretion inhibition, and specifically the effect of rabeprazole is less dependent on the method of administration and has less influence on the function of cytochrome P450. The effect of proton pump inhibitors, particularly the first generation, is modified by the genetic variety of the CYP2C19 enzyme and is significantly lower in rapid metabolisers. Proton pump inhibitors are very safe and immediate complications are rare. They can cause progression of gastritis in Helicobacter infection. In spite of causing hypergastrinemia, they do not have malignant potential. Their long-term administration is associated with an increased risk of pelvis and hip fractures, community-acquired pneumonia, and clostridium infection. They decrease the effect of antiaggregant therapy with clopidogrel, and increase the risk of recurrent cardiovascular events. This effect is not proven in prasugrel. We cannot expect any potential progression in developing new molecules or PPI formulas. The instructions for patients are usually not clearly presented and often lack important information. Keywords: proton pump inhibitors – omeprazole – lansoprazole – pantoprazole – rabeprazole – esomeprazole – side effects – interactions
- MeSH
- 2-Pyridinylmethylsulfinylbenzimidazoles pharmacology adverse effects therapeutic use MeSH
- Anti-Inflammatory Agents, Non-Steroidal adverse effects MeSH
- Cytochrome P-450 CYP2C19 genetics MeSH
- Eosinophilic Esophagitis drug therapy MeSH
- Esomeprazole pharmacology adverse effects therapeutic use MeSH
- Fractures, Bone chemically induced MeSH
- Gastroesophageal Reflux drug therapy MeSH
- Helicobacter Infections drug therapy MeSH
- Proton Pump Inhibitors * pharmacology adverse effects therapeutic use MeSH
- Clostridium Infections chemically induced MeSH
- Lansoprazole pharmacology adverse effects therapeutic use MeSH
- Drug Interactions MeSH
- Humans MeSH
- Misoprostol therapeutic use MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Omeprazole pharmacology adverse effects therapeutic use MeSH
- Pantoprazole MeSH
- Anti-Ulcer Agents pharmacology adverse effects therapeutic use MeSH
- Rabeprazole pharmacology adverse effects therapeutic use MeSH
- Stomach Ulcer drug therapy chemically induced prevention & control MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Hlavními medikamenty v léčbě acidopeptických onemocnění jsou inhibitory protonové pumpy (IPP). Všechny IPP jsou slabé zásady selektivně se metabolizující v kyselém prostředí a blokující funkci aktivní protonové pumpy. IPP poskytují účinnou léčbu u refluxní nemoci jícnu, eradikace Helicobacter pylori, funkční dyspepsie a gastropatie z nesteroidních antirevmatik. IPP se liší ve farmakokinetických charakteristikách, tyto rozdíly však nemusí mít klinicky relevantní důsledky. Účinnost IPP zejména první generace ovlivňuje genetická variabilita enzymu CYP2C19 a je významně nižší u rychlých metabolizátorů. IPP jsou velmi bezpečné a bezprostřední komplikace jsou výjimečné. U helikobakterové infekce vedou k progresi gastritidy. Přes hypergastrinemii nemají IPP maligní potenciál. Jejich dlouhodobé podávání je spojeno s vyšším rizikem fraktur páteře a kyčlí, komunitních pneumonií a klostridiové střevní infekce. Mohou vést ke snížení účinnosti antiagregační léčby s klopidogrelem se zvýšeným rizikem recidivujících kardiovaskulárních příhod. Příbalové letáky jsou vesměs nevhodně konstruovány a chybí v nich často zásadní informace.
Proton pump inhibitors are the most important medicines in the treatment of acid related diseases. All proton pump inhibitors are weak bases being selectively metabolised in the acid environment and blocking the function of active proton pumps. Proton pump inhibitors provide efficient treatment for gastroesophageal reflux disease, Helicobacter pylori eradication, functional dyspepsia and NSAID gastropathy. Proton pump inhibitors differ in pharmacokinetc properties but these differences do not necessarily have clinically relevant consequences. Generally, 2nd generation proton pump inhibitors provide faster onset of effect, longer gastric secretion inhibition, and specifically the effect of rabeprazole is less dependent on the method of administration and has less influence on the function of the cytochrome P450. The main effect of the 1st generation proton pump inhibitors is modified by the genetic variety of the enzyme CYP2C19 and it is significantly lower in rapid metabolizers. Proton pump inhibitors are very safe and immediate complications are exceptional. They can cause progression of gastritis in Helicobacter infection. In spite of hypergastrinemia they do not have malignant potential. Their long-lasting usage is associated with an increased risk of pelvis and hip fractures, community pneumonia, and clostridium infection. They decrease the effect of antiaggregant therapy with clopidogrel, and increase the risk of recurrent cardiovascular events. The instructions for patients are clearly presented and often important information is lacking. Key words: proton pump inhibitors – omeprazole – lansoprazole – pantoprazole – rabeprazole – esomeprazole – side effects – interactions The author declares he has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers. Submitted: 25. 7. 2013 Accepted: 12. 8. 2013
- MeSH
- Bacterial Infections MeSH
- Esomeprazole MeSH
- Gastrins drug effects MeSH
- Gastritis MeSH
- Helicobacter pylori drug effects MeSH
- Platelet Aggregation Inhibitors MeSH
- Proton Pump Inhibitors * pharmacology classification adverse effects therapeutic use MeSH
- Clinical Trials as Topic MeSH
- Lansoprazole MeSH
- Drug Interactions * MeSH
- Humans MeSH
- Meta-Analysis as Topic MeSH
- Intestinal Diseases MeSH
- Omeprazole pharmacology MeSH
- Pantoprazole MeSH
- Pneumonia etiology MeSH
- Rabeprazole MeSH
- Randomized Controlled Trials as Topic MeSH
- Practice Guidelines as Topic MeSH
- Cytochrome P-450 Enzyme System genetics MeSH
- Iron MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Byla provedena neintervenční studie s cílem zjistit výši dávek inhibitorů protonové pumpy v jednotlivých indikacích těchto léčiv. Do studie bylo zařazeno celkem 9071 pacientů, jejichž průměrný věk činil 56,23 ± 15,00 roku s mediánem 57 roků a jejichž průměrná tělesná hmotnost činila 79,38 ± 14,63 kg s mediánem 79 kg. Část pacientů zařazených do studie byla léčena nesteroidními protizánětlivými léčivy nebo kyselinou acetylsalicylovou (n = 3067), glukokortikoidy (n = 320), klopidogrelem (n = 217) nebo warfarinem (n = 806). Nejčastěji předepisovaným inhibitorem protonové pumpy je omeprazol, který byl ve všech indikacích podáván v průměrné dávce 24,04 ± 8,20 mg denně s mediánem dávky 20 mg denně. Průměrné dávky ostatních inhibitorů protonové pumpy (ve všech indikacích) činily v případě pantoprazolu 42,50 ± 10,96 mg denně s mediánem dávky 40 mg, v případě lansoprazolu 31,21 ± 9,84 mg denně s mediánem dávky 30 mg denně, v případě rabeprazolu 20,00 ± 4,33 mg denně s mediánem dávky 20 mg denně a v případě esomeprazolu 42,08 ± 16,78 mg denně s mediánem dávky 40 mg denně. Bylo též zjištěno, že výše dávek omeprazolu vysoce koreluje s tělesnou hmotností pacientů na vysoké hladině statistické významnosti.
A non-interventional study was conducted with the aim of determining the dosage of proton pump inhibitors in the individual indicat/ons of these drugs. A total of 9071 patients were enrolled in this study. Their average age was 56.23 ± 15.00 years, median 57 years. Their average body weight was 79.38 ± 14.63 kg, median 79 kg. Some of the patients included in the study were receiving treatment with non-steroidal anti-inflammatory drugs or acetylsalicylic acid (n = 3067), glucocorticoids (n = 320), clopidogrel (n = 217) or warfarin (n = 806). Omeprazole was the most frequently prescribed proton pump inhibitor and was administered in all indications at an average dose of 24.04 ± 8.20 mg daily, median dose 20 mg daily. The average doses of the other proton pump inhibitors (in all indications) were in the case of pantoprazole 42.50 ± 10.96 mg daily, median dose 40 mg; in the case of lansoprazole 31.21 ± 9.84 mg daily, median dose 30 mg daily; in the case of rabeprazole 20.00 ± 4.33 mg daily, median dose 20 mg daily and in the case of esomeprazole 42.08 ± 16.78 mg daily, median dose 40 mg daily. It was also shown that the dosage of omeprazole highly correlates with patient body weight, with this correlation reaching a high level of statistical significance.
- Keywords
- lansoprazol,
- MeSH
- 2-Pyridinylmethylsulfinylbenzimidazoles administration & dosage MeSH
- Epidemiologic Studies MeSH
- Esomeprazole administration & dosage MeSH
- Proton Pump Inhibitors * administration & dosage pharmacology MeSH
- Humans MeSH
- Omeprazole * administration & dosage MeSH
- Pantoprazole MeSH
- Rabeprazole MeSH
- Body Weight MeSH
- Dose-Response Relationship, Drug * MeSH
- Check Tag
- Humans MeSH
Comparative assessment of clinical efficiency of omeprazole and rabeprazole in treating gastroesophageal reflux disease (GERD). 65 patients with a verified diagnosis GERD were examined. Comparative clinical investigations of using of omeprazole and rabeprazole have revealed effectiveness of both drugs in the therapy of GERD. However, rabeprazole showed antisecretory action in the earlier periods, providing stable clinical remission of GERD and early scarring of erosive lesions of the esophageal mucosa, compared with omeprazole.
- MeSH
- Adult MeSH
- Gastroesophageal Reflux * therapy MeSH
- Endoscopy, Gastrointestinal MeSH
- Proton Pump Inhibitors classification therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Omeprazole * administration & dosage therapeutic use MeSH
- Rabeprazole * administration & dosage therapeutic use MeSH
- Comparative Effectiveness Research MeSH
- Statistics as Topic MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Keywords
- lansoprazol, refluxní choroba jícnu,
- MeSH
- Anti-Inflammatory Agents, Non-Steroidal MeSH
- Dyspepsia drug therapy MeSH
- Esomeprazole MeSH
- Gastrins MeSH
- Gastritis, Atrophic MeSH
- Gastroesophageal Reflux drug therapy MeSH
- Helicobacter pylori pathogenicity MeSH
- Inflammatory Bowel Diseases MeSH
- Helicobacter Infections drug therapy MeSH
- Proton Pump Inhibitors history pharmacology therapeutic use MeSH
- Carcinoma MeSH
- Colorectal Neoplasms MeSH
- Drug Interactions MeSH
- Humans MeSH
- Malabsorption Syndromes MeSH
- Stomach Neoplasms MeSH
- Stomach Diseases drug therapy MeSH
- Omeprazole pharmacology chemical synthesis therapeutic use MeSH
- Pantoprazole MeSH
- Peptic Ulcer drug therapy MeSH
- Polyps drug therapy MeSH
- Rabeprazole MeSH
- Risk MeSH
- Vitamin B 12 MeSH
- Stomach microbiology pathology drug effects MeSH
- Check Tag
- Humans MeSH
Článek pojednává o historii a současném použití inhibitorů protonové pumpy (IPP) jako nejúčinnějších léků, které blokují sekreci žaludeční kyseliny. IPP se i u nás pomalu stávají léky volně prodejnými, což zvýší jejich dostupnost i pro pacienty, kteří mají příznaky spíše lehké a nechtějí navštívit lékaře. Indikací k tomuto volnému prodeji jsou právě refluxní příznaky (pyróza, regurgitace), proto je této indikaci věnována největší pozornost.
The article deals with history and present use of proton pump inhibitors (PPI), the most effective drugs, which block secretion of gastric acid. In the Czech Republic PPI slowly become OTC drugs, that increases their availability for patients, who have slight symptoms and do not want to visit doctor. Indications for OTC are just reflux symptoms (pyrosis, regurgitation) therefore the biggest attention is paid to their indication.
- MeSH
- Esomeprazole MeSH
- Gastroesophageal Reflux drug therapy MeSH
- Proton Pump Inhibitors administration & dosage pharmacokinetics therapeutic use MeSH
- Lansoprazole MeSH
- Drug Interactions MeSH
- Humans MeSH
- Omeprazole pharmacokinetics therapeutic use MeSH
- Pantoprazole MeSH
- Heartburn drug therapy MeSH
- Rabeprazole MeSH
- Check Tag
- Humans MeSH
- Keywords
- ezomeprazol,
- MeSH
- 2-Pyridinylmethylsulfinylbenzimidazoles pharmacology MeSH
- Helicobacter Infections drug therapy MeSH
- Proton Pump Inhibitors pharmacokinetics pharmacology classification MeSH
- Lansoprazole MeSH
- Humans MeSH
- Omeprazole analogs & derivatives pharmacology MeSH
- Pantoprazole MeSH
- Rabeprazole MeSH
- Gastric Juice drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
